Measurements of chlorhexidine, p-chloroaniline, and p-chloronitrobenzene in saliva after mouth wash before and after operation with 0.2% chlorhexidine digluconate in maxillofacial surgery: a randomised controlled trial

H. Below, O. Assadian, R. Baguhl, U. Hildebrandt, B. Jäger, K. Meissner, D. J. Leaper, Axel Kramer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Chlorhexidine gluconate is used to prevent the accumulation of dental plaque and gingivitis, infection of the surgical site, and ventilator-associated pneumonia in maxillofacial surgery, but it is not clear whether the metabolites of chlorhexidine are detectable in the patient's saliva at clinically relevant concentrations. Forty-three patients who had orofacial operations were randomised to use a 0.2% chlorhexidine gluconate (n = 23), or an octenidine-based, chlorhexidine-free (n = 20), mouthwash once preoperatively and three times daily for five postoperative days. After the first, 8.7 (23.3) mg/L chlorhexidine (0.7%-2.5% of the total amount used) was measured in saliva. The concentration increased to 15.2 (6.2) mg/L after the second rinse (first postoperative day), and peaked at 29.4 (11.2) mg/L on the fourth postoperative day. It remained detectable for up to 12 hours after the last one, but was not detectable in serum or urine at any time. The potentially carcinogenic metabolite p-chloroaniline was detectable in saliva at higher concentrations in the chlorhexidine group (0.55 mg/L) than the octenidine group (0.21 mg/L), and p-chloronitrobenzene was detected in both groups in only minimal concentrations (0.001-0.21 mg/L). Chlorhexidine gluconate mouthwashes do increase the concentration of p-chloroaniline, but a single use seems to be safe. Whether prolonged exposure over many years may have carcinogenic potential is still not clear. Based on the hitherto unknown kinetics of p-chloroaniline in saliva, the recent recommendation of the Federal Drug Administration (FDA) in the USA to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months seems to be justified.

LanguageEnglish
Pages150-155
Number of pages6
JournalBritish Journal of Oral and Maxillofacial Surgery
Volume55
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

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octenidine
Chlorhexidine
Oral Surgery
Mouthwashes
Saliva
Mouth
Randomized Controlled Trials
Surgical Wound Infection
Ventilator-Associated Pneumonia
Dental Plaque
Gingivitis
Urine
4-chloroaniline
chlorhexidine gluconate
4-chloronitrobenzene
Serum
Pharmaceutical Preparations

Cite this

@article{ff17d7d58b9b4648916bb703f9b157aa,
title = "Measurements of chlorhexidine, p-chloroaniline, and p-chloronitrobenzene in saliva after mouth wash before and after operation with 0.2{\%} chlorhexidine digluconate in maxillofacial surgery: a randomised controlled trial",
abstract = "Chlorhexidine gluconate is used to prevent the accumulation of dental plaque and gingivitis, infection of the surgical site, and ventilator-associated pneumonia in maxillofacial surgery, but it is not clear whether the metabolites of chlorhexidine are detectable in the patient's saliva at clinically relevant concentrations. Forty-three patients who had orofacial operations were randomised to use a 0.2{\%} chlorhexidine gluconate (n = 23), or an octenidine-based, chlorhexidine-free (n = 20), mouthwash once preoperatively and three times daily for five postoperative days. After the first, 8.7 (23.3) mg/L chlorhexidine (0.7{\%}-2.5{\%} of the total amount used) was measured in saliva. The concentration increased to 15.2 (6.2) mg/L after the second rinse (first postoperative day), and peaked at 29.4 (11.2) mg/L on the fourth postoperative day. It remained detectable for up to 12 hours after the last one, but was not detectable in serum or urine at any time. The potentially carcinogenic metabolite p-chloroaniline was detectable in saliva at higher concentrations in the chlorhexidine group (0.55 mg/L) than the octenidine group (0.21 mg/L), and p-chloronitrobenzene was detected in both groups in only minimal concentrations (0.001-0.21 mg/L). Chlorhexidine gluconate mouthwashes do increase the concentration of p-chloroaniline, but a single use seems to be safe. Whether prolonged exposure over many years may have carcinogenic potential is still not clear. Based on the hitherto unknown kinetics of p-chloroaniline in saliva, the recent recommendation of the Federal Drug Administration (FDA) in the USA to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months seems to be justified.",
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Measurements of chlorhexidine, p-chloroaniline, and p-chloronitrobenzene in saliva after mouth wash before and after operation with 0.2% chlorhexidine digluconate in maxillofacial surgery : a randomised controlled trial. / Below, H.; Assadian, O.; Baguhl, R.; Hildebrandt, U.; Jäger, B.; Meissner, K.; Leaper, D. J.; Kramer, Axel.

In: British Journal of Oral and Maxillofacial Surgery, Vol. 55, No. 2, 01.02.2017, p. 150-155.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Measurements of chlorhexidine, p-chloroaniline, and p-chloronitrobenzene in saliva after mouth wash before and after operation with 0.2% chlorhexidine digluconate in maxillofacial surgery

T2 - British Journal of Oral and Maxillofacial Surgery

AU - Below, H.

AU - Assadian, O.

AU - Baguhl, R.

AU - Hildebrandt, U.

AU - Jäger, B.

AU - Meissner, K.

AU - Leaper, D. J.

AU - Kramer, Axel

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Chlorhexidine gluconate is used to prevent the accumulation of dental plaque and gingivitis, infection of the surgical site, and ventilator-associated pneumonia in maxillofacial surgery, but it is not clear whether the metabolites of chlorhexidine are detectable in the patient's saliva at clinically relevant concentrations. Forty-three patients who had orofacial operations were randomised to use a 0.2% chlorhexidine gluconate (n = 23), or an octenidine-based, chlorhexidine-free (n = 20), mouthwash once preoperatively and three times daily for five postoperative days. After the first, 8.7 (23.3) mg/L chlorhexidine (0.7%-2.5% of the total amount used) was measured in saliva. The concentration increased to 15.2 (6.2) mg/L after the second rinse (first postoperative day), and peaked at 29.4 (11.2) mg/L on the fourth postoperative day. It remained detectable for up to 12 hours after the last one, but was not detectable in serum or urine at any time. The potentially carcinogenic metabolite p-chloroaniline was detectable in saliva at higher concentrations in the chlorhexidine group (0.55 mg/L) than the octenidine group (0.21 mg/L), and p-chloronitrobenzene was detected in both groups in only minimal concentrations (0.001-0.21 mg/L). Chlorhexidine gluconate mouthwashes do increase the concentration of p-chloroaniline, but a single use seems to be safe. Whether prolonged exposure over many years may have carcinogenic potential is still not clear. Based on the hitherto unknown kinetics of p-chloroaniline in saliva, the recent recommendation of the Federal Drug Administration (FDA) in the USA to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months seems to be justified.

AB - Chlorhexidine gluconate is used to prevent the accumulation of dental plaque and gingivitis, infection of the surgical site, and ventilator-associated pneumonia in maxillofacial surgery, but it is not clear whether the metabolites of chlorhexidine are detectable in the patient's saliva at clinically relevant concentrations. Forty-three patients who had orofacial operations were randomised to use a 0.2% chlorhexidine gluconate (n = 23), or an octenidine-based, chlorhexidine-free (n = 20), mouthwash once preoperatively and three times daily for five postoperative days. After the first, 8.7 (23.3) mg/L chlorhexidine (0.7%-2.5% of the total amount used) was measured in saliva. The concentration increased to 15.2 (6.2) mg/L after the second rinse (first postoperative day), and peaked at 29.4 (11.2) mg/L on the fourth postoperative day. It remained detectable for up to 12 hours after the last one, but was not detectable in serum or urine at any time. The potentially carcinogenic metabolite p-chloroaniline was detectable in saliva at higher concentrations in the chlorhexidine group (0.55 mg/L) than the octenidine group (0.21 mg/L), and p-chloronitrobenzene was detected in both groups in only minimal concentrations (0.001-0.21 mg/L). Chlorhexidine gluconate mouthwashes do increase the concentration of p-chloroaniline, but a single use seems to be safe. Whether prolonged exposure over many years may have carcinogenic potential is still not clear. Based on the hitherto unknown kinetics of p-chloroaniline in saliva, the recent recommendation of the Federal Drug Administration (FDA) in the USA to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months seems to be justified.

KW - absorption

KW - antiseptic mouthwash

KW - Chlorhexidine

KW - p-chloroaniline

KW - saliva

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U2 - 10.1016/j.bjoms.2016.10.007

DO - 10.1016/j.bjoms.2016.10.007

M3 - Article

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SP - 150

EP - 155

JO - British Journal of Oral and Maxillofacial Surgery

JF - British Journal of Oral and Maxillofacial Surgery

SN - 0266-4356

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ER -